Browsing by Author "Miranda, Marina Barcelos de"

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    Brazilian green propolis hydroalcoholic extract as a therapeutic adjuvant to treat cutaneous leishmaniasis.
    (2020) Cunha, Beatriz Carvalho; Miranda, Marina Barcelos de; Afonso, Luís Carlos Crocco; Abreu, Sheila Rago Lemos; Testasicca, Miriam Conceição de Souza; Silva, Gisele Rodrigues da; Moura, Sandra Aparecida Lima de
    Cutaneous leishmaniasis is caused by Leishmania parasites. There are a limited number of drugs to treat the cutaneous leishmaniasis, and most of them cause severe adverse effects. Therefore, new therapeutic strategies to treat cutaneous leishmaniasis should be developed. In this study, a standardized Brazilian green propolis (BGP) hydroalcoholic extract (Cytopropolis®, Nectar Pharma Brazil) was evaluated as a therapeutic adjuvant, aiming at the treatment of cutaneous leishmaniasis. The antileishmanial effects of different concentrations of BGP hydroalcoholic extract (500, 250, 125, 62.5, 31.25, 15.6, 7.8, and 3.9 µg ml−1) were determined in vitro against amastigotes and promastigotes and in a murine model of leishmaniasis. High concentrations of BGP hydroalcoholic extract (500, 250, 125, and 62.5 µg ml−1) reduced the viability of promastigotes. All concentrations acted against amastigotes. BGP hydroalcoholic extract (500 and 250 µg ml−1) decreased the number of promastigotes in macrophages. In addition, after 2 weeks of oral treatment, BGP hydroalcoholic extract (250 mg/kg/day) decreased the parasites and induced the macrophage infiltration in the lesion caused by the Leishmania amazonensis on the paw of mice. BGP hydroalcoholic extract may represent a therapeutic adjuvant to treat cutaneous leishmaniasis.
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    Efeitos da administração do extrato hidroalcóolico de propólis verde no processo inflamatório de camundongos submetidos a dieta hipoproteica.
    (2018) Miranda, Marina Barcelos de; Moura, Sandra Aparecida Lima de; Moura, Sandra Aparecida Lima de; Silva, Albená Nunes da; Nogueira, Katiane de Oliveira Pinto Coelho
    Inflamação e desnutrição, quando ocorrem de forma associada, são consideradas um fator agravante do risco de morbimortalidade no ambiente clínico. Em função disto, há uma busca incessante por novas terapias como possíveis estratégiasterapêuticas para modular a inflamação crônica. Dentre estas estratégias, uma que se destaca é a própolis verde. A própolis verde é um produto natural, produzido pelas abelhas Apis melliferas, cuja espécie fornecedora da resina é a Baccharis dracunculifolia. Apesar das suas ações já evidenciadas pela literatura, não há esclarecimentos sobre o efeito antiinflamatório da própolis verde frente a um estado nutricional comprometido. Neste trabalho, propomos caracterizar os efeitos da administração do extrato hidroalcoólico da própolis verde no processo inflamatório crônico de animais submetidos a dieta hipoproteica. Foram utilizados 80 camundongos, divididos aleatoriamente em 8 grupos, considerando-se dois tempos de implantação e administração da própolis (7 e 15 dias): dieta normoproteica tratamento controle (NC); dieta normoproteica tratamento com própolis (NP); dieta hipoproteica tratamento controle (HC); dieta hipoproteica tratamento com própolis (HP). Foram ofertadas dietas artesanais com 3% (hipoproteica) e 12% de proteína (normoproteica), durante todo o período experimental. Na 4ª semana da dieta, realizou-se o procedimento cirúrgico para a implantação subcutânea das esponjas nos animais e indução da resposta inflamatória. Neste mesmo momento foi iniciada a administração diária, via oral, do extrato hidroalcoólico da própolis verde, na dose de 500mg/kg aos grupos tratados. A eutanásia ocorreu pós 7 e 15 dias da implantação das esponjas. Os resultados indicam que os animais que receberam a dieta hipoproteica em ambos os tempos avaliados, apresentaram uma redução significativa de peso corporal e ainda houve uma redução de proteínas totais séricas no tempo de 15 dias, no grupo HC. Os parâmetros hematológicos demonstraram que os animais que receberam a própolis, grupos NP e HP, sofreram alterações significativas nos valores de eritrócitos, hemoglobina e hematócritos, entretanto, os animais nutridos e tratados com própolis (NP) foram capazes de restabelecer estes valores no tempo de 15 dias. O tratamento com própolis também alterou níveis circulantes de plaquetas, monócitos e eosinófilos. A contagem de vasos nas esponjas implantadas revela, no tempo de 7 dias, uma maior contagem nos grupos com dieta hipoproteica (HC e HP); enquanto que, no tempo de 15 dias, houve uma menor contagem nos grupos tratados com própolis (NP e HP). A análise dos parâmetros inflamatórios, análise histopatológica, contagem total de células no microambiente das espojas e a dosagem dos níveis da citocinas TNF-α, indicaram que os grupos tratados com própolis apresentaram significativa redução de infiltrado inflamatório em ambos os tempos e aumento de TNF-α no tempo de 7 dias. Conclui-se portanto, que o extrato hidroalcoólico da própolis verde exerceu atividade sobre peso, parâmetros hematológicos e leucocitário, perfil proteico, e ainda, ação antiangiogênica e antiinflamatória nos grupos com dieta normoproteica e hipoproteica, mas neste último, com menos eficácia.
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    Hydroalcoholic extract of Brazilian green propolis modulates inflammatory process in mice submitted to a low protein diet.
    (2019) Miranda, Marina Barcelos de; Lanna, Mariana Ferreira; Nascimento, Ana Luiza Barros; Paula, Carmen Aparecida de; Silva, Marcelo Eustáquio; Silva, Mariane Felipetto da; Barcelos, Luciola da Silva; Moura, Sandra Aparecida Lima de
    The occurrence of inflammation and protein malnutrition is an aggravating risk factor for morbidity and mortality in the clinical setting. The green propolis, a natural product made by Apis mellifera bees from Baccharis dracunculifolia resin, has therapeutic potential to modulate chronic inflammation. However, its effect on inflammation in an impaired nutritional status is not known. The aim of this study was to characterize the effects of the administration of the hydroalcoholic extract of the green propolis in the chronic inflammatory process of mice submitted to a low-protein diet. For this, we used the subcutaneous implantation of sponge disks as an inflammatory model and the animals were distributed in the following groups: standard protein diet (12% protein content), control treatment; standard protein diet, propolis treatment; low-protein diet (3% protein content), control treatment; low-protein diet, propolis treatment. Propolis was given daily at a dose of 500 mg/kg (p.o.) during a period of 7 or 15 days. Our main findings show that animals fed with standard protein diet and treated with propolis had low levels of red blood cells, hemoglobin, and hematocrit, with the subsequent reestablishment of these levels, in addition to monocyte count elevation and higher TNF levels after one week of treatment. In the low-protein diet group, the propolis treatment provided a significant recovery in weight and maintenance of total serum protein levels at the end of two weeks of treatment. Histological analysis showed propolis reduced the inflammatory infiltrate in the sponges of both standard and low-protein diet groups. In addition, the propolis extract presented antiangiogenic effect in both groups. Therefore, our data suggests that the hydroalcoholic extract of the green propolis promotes weight recovery and avoid the reduction of protein levels, in addition to inhibit inflammation and angiogenesis in animals fed with a low-protein diet.
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    Kinetics of phenotypic and functional changes in mouse models of sponge implants : rational selection to optimize protocols for specific biomolecules screening purposes.
    (2020) Lanna, Mariana Ferreira; Resende, Lucilene Aparecida; Soares, Rodrigo Dian de Oliveira Aguiar; Miranda, Marina Barcelos de; Mendonça, Ludmila Zanandreis de; Melo Júnior, Otoni Alves de Oliveira; Mariano, Reysla Maria da Silveira; Leite, Jaqueline Costa; Silveira, Patricia; Oliveira, Rodrigo Corrêa de; Dutra, Walderez Ornelas; Reis, Alexandre Barbosa; Martins Filho, Olindo Assis; Moura, Sandra Aparecida Lima de; Lemos, Denise da Silveira; Giunchetti, Rodolfo Cordeiro
    The sponge implant has been applied as an important in vivo model for the study of inflammatory processes as it induces the migration, proliferation, and accumulation of inflammatory cells, angiogenesis, and extracellular matrix deposition in its trabeculae. The characterization of immune events in sponge implants would be useful in identifying the immunological events that could support the selection of an appropriate experimental model (mouse strain) and time post-implant analysis in optimized protocols for novel applications of this model such as in biomolecules screening. Here, the changes in histological/morphometric, immunophenotypic and functional features of infiltrating leukocytes (LEU) were assessed in sponge implants for Swiss, BALB/c, and C57BL/6 mice. A gradual increase of fibrovascular stroma and a progressive decrease in LEU infiltration, mainly composed of polymorphonuclear cells with progressive shift toward mononuclear cells at late time-points were observed over time. Usually, Swiss mice presented a more prominent immune response with late mixed pattern (pro-inflammatory/anti-inflammatory: IL-2/IFN-γ/IL-4/IL-10/IL-17) of cytokine production. While BALB/c mice showed an early activation of the innate response with a controlled cytokine profile (low inflammatory potential), C57BL/6 mice presented a typical early pro-inflammatory (IL-6/TNF/IFN-γ) response with persistent neutrophilic involvement. A rational selection of the ideal time-point/mouse-lineage would avoid bias or tendentious results. Criteria such as low number of increased biomarkers, no recruitment of cytotoxic response, minor cytokine production, and lower biomarker connectivity (described as biomarker signature analysis and network analysis) guided the choice of the best time-point for each model (Day5/Swiss; Day7/BALB/c; Day6/C57BL/6) with wide application for screening purposes, such as identification of therapeutic biomolecules, selection of antigens/adjuvants, and follow-up of innate and adaptive immune response to vaccines candidates.
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    Methotrexate locally released from poly (caprolactone) implants : inhibition of the inflammatory angiogenesis response in a murine sponge model and the absence of systemic toxicity.
    (2015) Oliveira, Leandro Gonzaga de; Figueiredo, Letícia Aparecida; Cunha, Gabriella Maria Fernandes; Oliveira, Laser Antônio Machado de; Miranda, Marina Barcelos de; Silva, Gisele Rodrigues da; Moura, Sandra Aparecida Lima de
    In this study, the methotrexate (MTX) was incorporated into the poly(-caprolactone) (PCL) to design implants (MTX PCL implants) aiming the local treatment of inflammatory angiogenesis diseases without causing systemic side effects. Sponges were inserted into the subcutaneous tissue of mice as a framework for fibrovascular tissue growth. After 4 days, MTX PCL implants were also introduced, and anti-inflammatory, antiangiogenic, and antifibrogenic activities of the MTX were determined. MTX reduced the vascularization (hemoglobin content), the neutrophil, and monocyte/macrophage infiltration (MPO and NAG activities, respectively), and the collagen deposition in sponges. MTX reduced tumor necrosis factor-_ and IL-6 levels, demonstrating its local antiangiogenic and anti-inflammatory effects. Furthermore, hepatotoxicity, nephrotoxicity, and myelotoxicity, which could be induced by the drug, were evaluated. However, MTX did not promote toxicity to these organs, as the levels of AST and ALT (hepatic markers) and creatinine and urea (renal markers) were not increased, and the complete blood count was not decreased. In conclusion, MTX PCL implants demonstrated to be effective in regulating the components of the inflammatory angiogenesis locally established, and presented an acceptable safety profile. C _ 2015Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci.
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    Tacrolimus delivered from polymeric implants suppressed inflammation and angiogenesis in vivo without inducing nephrotoxicity, hepatotoxicity, and myelosuppression.
    (2018) Oliveira, Leandro Gonzaga de; Miranda, Marina Barcelos de; Moura, Sandra Aparecida Lima de; Silva, Gisele Rodrigues da
    Implants containing tacrolimus and poly(ɛ-caprolactone) (tacrolimus PCL implants) were designed to release the drug directly into the inflammatory and angiogenesis site without inducing systemic toxicity. A non-biocompatible sponge, inserted into the subcutaneous tissue of mice, functioned as a frame for inducing inflammatory and angiogenic responses. After 4 days post-insertion of sponges, PCL implants loaded with tacrolimus were inserted adjacent to the pathological site, and the cellular and molecular components of inflammation were monitored. PCL implants constantly released tacrolimus into the target site. Tacrolimus limited the expression of TNF-α, a pro-angiogenic and pro-inflammatory cytokine. As a result, the neovascularization was inhibited. It also limited the neutrophil migration at the early stage of inflammation and the monocyte/macrophage infiltration at the proliferative phase due to the reduced activities of myeloperoxidase (MPO) and N-Acetyl-β-D-Glucosaminidase (NAG), respectively. Tacrolimus released from PCL implants did not induce toxicity in the liver and kidney, since the biomarkers of functionality of these organs showed normal levels. In addition, the drug did not promote myelosuppression. It was suggested that the controlled tacrolimus release from implantable devices directly into the pathological site could provide the remission of the inflammatory and angiogenic responses without carrying out organ toxicity.
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    Vasoactive intestinal peptide reduces the inflammatory profile in mice infected with Trypanosoma cruzi.
    (2015) Higyno, Pulchéria Maria Silva; Mendes, Priscila Fagundes; Miranda, Marina Barcelos de; Pereira, Dario Elias; Mota, Ana Paula Lucas; Nogueira, Katiane de Oliveira Pinto Coelho; Caldas, Ivo Santana; Moura, Sandra Aparecida Lima de; Menezes, Cristiane Alves da Silva
    Vasoactive intestinal peptide (VIP) has gained great prominence because of its therapeutic potential, which is ascribed to its ability to regulate innate immunity, inhibit antigen-specific Th1 cell responses, and generate T regulatory cells. Additionally, VIP may act as a natural antimicrobial peptide, killing bacteria, fungi, and infective forms of Trypanosoma brucei. Despite the possible relevance of VIP during the course of Chagas disease, studies regarding this in human and experimental Trypanosoma cruzi infections remain poorly characterized. In this work, we evaluated the effects of VIP on systemic and cardiac immune responses during experimental acute infection. C57BL/6 mice were infected with 5000 trypomastigotes of the VL-10 strain of T. cruzi and treated with intraperitoneal VIP injection every other day for one month. After 30 days, we observed no reduction in parasitemia levels. However, we observed a reduction in serum levels of IFN-gamma and IL-2 and an increase in that of IL-4. These data suggest that VIP treatment modified immune responses to favor the Th2 response, which had no impact on parasitemia levels although the serum level of IFN-gamma was reduced. However, this change in immune balance reduced heart damage, as noted by the smaller cardiac volume and the moderate inflammatory.